A Practical Synthesis of Macrocyclic Schiff Base Bearing Hydroxyethyl Pendants Utilizing Solubility Discrepancies

Six macrocyclic Schiff bases bearing hydroxyethyl pendants have been synthesized in high yields via [2 + 2] condensation between the rigid dialdehydes and 2-[bis(2-aminoethyl)amino]ethanol or 1-[bis(2-aminoethyl)amino]-2-propanol at 0 oC for 12 hours in the CH3CN/H2O mixture. Solubility discrepancies between macrocyclic products and raw materials in selected solvents enable a facile separation and high yields, avoiding any intractable chromatographic purification. This straightforward synthetic protocol provides a relatively facile resolution with potential widespread applications for the synthesis of Schiff bases.

Green Chemistry: Air-Triggered Catalyst- and Oxidant-Free Decarboxylative Oxysulfonylation of Arylpropiolic Acids With Sodium Sulfinates

The exploration of novel green synthetic strategies to obtain useful organic molecules is one of the most important missions for sustainable development. Herein, an efficient and sustainable decarboxylative oxysulfonylation between arylpropiolic acids and sodium sulfinates has been established, providing a broad scope of β-ketosulfones in excellent yields. The reactions proceed at room temperature employing air as the only oxidant and oxygen source without extra catalyst, oxidant, and additive. Additionally, the reaction is scalable, and the products have been easily isolated by simple recrystallization, avoiding the chromatographic purification. Mechanistic studies have also been conducted to reveal that the reaction proceed via a radical mechanism.

Chromatography-Free Purification Strategies for Large Biological Macromolecular Complexes Involving Fractionated PEG Precipitation and Density Gradients

A complex interplay between several biological macromolecules maintains cellular homeostasis. Generally, the demanding chemical reactions which sustain life are not performed by individual macromolecules, but rather by several proteins that together form a macromolecular complex. Understanding the functional interactions amongst subunits of these macromolecular machines is fundamental to elucidate mechanisms by which they maintain homeostasis. As the faithful function of macromolecular complexes is essential for cell survival, their mis-function leads to the development of human diseases. Furthermore, detailed mechanistic interrogation of the function of macromolecular machines can be exploited to develop and optimize biotechnological processes. The purification of intact macromolecular complexes is an essential prerequisite for this; however, chromatographic purification schemes can induce the dissociation of subunits or the disintegration of the whole complex. Here, we discuss the development and application of chromatography-free purification strategies based on fractionated PEG precipitation and orthogonal density gradient centrifugation that overcomes existing limitations of established chromatographic purification protocols. The presented case studies illustrate the capabilities of these procedures for the purification of macromolecular complexes.

Chemical and Biological Aspects of Secondary Metabolites from Tongan Marine Sponges

<p>This thesis describes the isolation and structural elucidation of 17 new secondary metabolites from Tongan marine sponges including examples of alkaloids, polyketides and terpenoids. In the process of this work, 19 sponge specimens were subjected to preliminary NMR-guided investigation. Nine organisms were selected for further analysis on the basis of the structural novelty perceived within the HMBC spectrum of crude fractions generated by the first chromatographic purification of their crude extracts, and the apparent rarity of the specimen. Investigation of two different demosponge specimens afforded the γ-hydroxybutenolide sesterterpenes (23 and 24), and small quantities of the potently cytotoxic alkaloid 14-bromohomofascaplysin (29). The analysis of two samples of a dictyoceratid sponge yielded the new labdane diterpenes luakuliides A–C (33–36), characterised by a bridging hemi-acetal function on the B-ring of the labdane bicycle. Luakuliide A (33) and its methyl acetal derivative 34 were found to display interesting immunomodulatory activity. Seven new α-pyrone polyketides, lehualides E–K (69–75), were isolated from a Plakortis sp. Lehualides H–K (72–75) display a range of sulfur functionalities, the natures of which were determined by spectroscopic comparison with synthesised model compounds. Another plakinid sponge specimen contained four new polyketides (95–98), all of which possess different cyclic peroxide moieties. Cyclic peroxides 95, 97 and 98 displayed potent cytoxicity against human promyelocytic leukemia cells (HL- 60). Chemical genetic and phenoytypic profiling studies of 95 were undertaken in Saccharomyces cerevisiae yeast using the homozygous diploid and heterozygous diploid deletion libraries. These studies indicate that 95 acts to disrupt Ca2+ homeostasis, leading to elevation of intracellular Ca2 levels.</p>

Chemical and Biological Aspects of Secondary Metabolites from Tongan Marine Sponges

<p>This thesis describes the isolation and structural elucidation of 17 new secondary metabolites from Tongan marine sponges including examples of alkaloids, polyketides and terpenoids. In the process of this work, 19 sponge specimens were subjected to preliminary NMR-guided investigation. Nine organisms were selected for further analysis on the basis of the structural novelty perceived within the HMBC spectrum of crude fractions generated by the first chromatographic purification of their crude extracts, and the apparent rarity of the specimen. Investigation of two different demosponge specimens afforded the γ-hydroxybutenolide sesterterpenes (23 and 24), and small quantities of the potently cytotoxic alkaloid 14-bromohomofascaplysin (29). The analysis of two samples of a dictyoceratid sponge yielded the new labdane diterpenes luakuliides A–C (33–36), characterised by a bridging hemi-acetal function on the B-ring of the labdane bicycle. Luakuliide A (33) and its methyl acetal derivative 34 were found to display interesting immunomodulatory activity. Seven new α-pyrone polyketides, lehualides E–K (69–75), were isolated from a Plakortis sp. Lehualides H–K (72–75) display a range of sulfur functionalities, the natures of which were determined by spectroscopic comparison with synthesised model compounds. Another plakinid sponge specimen contained four new polyketides (95–98), all of which possess different cyclic peroxide moieties. Cyclic peroxides 95, 97 and 98 displayed potent cytoxicity against human promyelocytic leukemia cells (HL- 60). Chemical genetic and phenoytypic profiling studies of 95 were undertaken in Saccharomyces cerevisiae yeast using the homozygous diploid and heterozygous diploid deletion libraries. These studies indicate that 95 acts to disrupt Ca2+ homeostasis, leading to elevation of intracellular Ca2 levels.</p>

Natural Products Studies of Marine Organisms of the South Pacific

<p>This thesis describes the NMR-guided isolation and structural elucidation of one novel and several known compounds from marine organisms collected from Tonga and New Zealand. In the process of this work, 11 Tongan algal specimens were subjected to preliminary NMR-guided investigation, as the study of Tongan marine algae is poorly represented. The HMBC spectra of crude fractions generated by the first chromatographic purification of the crude extracts were analysed for perceived structural novelty, providing three specimens that warranted further investigation. Investigation of unknown algae PTN4_17G afforded substructure 76, observed in the known compound avrainvilloside, which included the rare 6-deoxy-6-aminoglucose moiety. This aminoglucose moiety has been reported from marine sources only twice in literature, both in algae specimens. An investigation of unknown brown algae PTN4_18E afforded substructure 83, a methacrylic acid containing moiety. Methacrylic acid moieties are also uncommon in marine organisms, with 27 reported structures containing the moiety, of which only two occur from algae. In each case suitable, mass spectrometry data was not obtainable therefore full structural elucidation of the compounds was not achieved. Further analysis of the unknown algae PTN3_38C afforded the known compound fistularin-3 86, although further studies revealed that a sponge contaminant was responsible for the presence of the compound. The results of this algae study provided interesting correlations between secondary metabolite concentrations of algae in temperate and sub-tropical environments, contrary to the observed correlations of marine sponges. An investigation into an unknown New Zealand Raspailia sponge was conducted as previous studies had suggested the presence of novel resonances. Further analysis of the specimen yielded the known clerodane raspailodane A 126 and the unexpected novel steroidal glycoside raspailoside A 135. Biological activity studies conducted on raspailoside A showed inactivity towards the mammalian cell line HL-60 and Saccharomyces cerevisiae assays.</p>

Natural Products Studies of Marine Organisms of the South Pacific

<p>This thesis describes the NMR-guided isolation and structural elucidation of one novel and several known compounds from marine organisms collected from Tonga and New Zealand. In the process of this work, 11 Tongan algal specimens were subjected to preliminary NMR-guided investigation, as the study of Tongan marine algae is poorly represented. The HMBC spectra of crude fractions generated by the first chromatographic purification of the crude extracts were analysed for perceived structural novelty, providing three specimens that warranted further investigation. Investigation of unknown algae PTN4_17G afforded substructure 76, observed in the known compound avrainvilloside, which included the rare 6-deoxy-6-aminoglucose moiety. This aminoglucose moiety has been reported from marine sources only twice in literature, both in algae specimens. An investigation of unknown brown algae PTN4_18E afforded substructure 83, a methacrylic acid containing moiety. Methacrylic acid moieties are also uncommon in marine organisms, with 27 reported structures containing the moiety, of which only two occur from algae. In each case suitable, mass spectrometry data was not obtainable therefore full structural elucidation of the compounds was not achieved. Further analysis of the unknown algae PTN3_38C afforded the known compound fistularin-3 86, although further studies revealed that a sponge contaminant was responsible for the presence of the compound. The results of this algae study provided interesting correlations between secondary metabolite concentrations of algae in temperate and sub-tropical environments, contrary to the observed correlations of marine sponges. An investigation into an unknown New Zealand Raspailia sponge was conducted as previous studies had suggested the presence of novel resonances. Further analysis of the specimen yielded the known clerodane raspailodane A 126 and the unexpected novel steroidal glycoside raspailoside A 135. Biological activity studies conducted on raspailoside A showed inactivity towards the mammalian cell line HL-60 and Saccharomyces cerevisiae assays.</p>

Indium(III)-Catalyzed Synthesis of Primary Carbamates and N-Substituted Ureas

An indium triflate-catalyzed synthesis of primary carbamates from alcohols and urea as an ecofriendly carbonyl source has been developed. Various linear, branched, and cyclic alcohols were converted into the corresponding carbamates in good to excellent yields. This method also provided access to N-substituted ureas by carbamoylation of amines. All the products were obtained by simple filtration or crystallization, without the need for chromatographic purification. Mechanistic investigations suggest that the carbamoylation reaction proceeds through activation of urea by O-coordination with indium, followed by nucleophilic attack by the alcohol or amine on the carbonyl center of urea. The inexpensive and easily available starting materials and catalyst, the short reaction times, and the ease of product isolation highlight the inherent practicality of the developed method.

A New Pentacyclic Triterpenoid from Albizia lebbekoides (DC) Benth (Leguminosae)

Albizia lebbekoides (DC) Benth is one of the five species of the genus Albizia found in the Philippines. Not much is known about the chemistry and potential uses of this species. Solvent partition followed by sequential and repeated liquid chromatographic purification over silica led to the isolation of a compound from the hexane extract of A. lebbekoides leaves. A review of related literature and spectral analyses showed that the isolated compound is a new pentacyclic triterpenoid with an oleanane skeleton. Its structure was determined as 3β, 16α-dihydroxyolean-6(7),12(13)-dien-28-oic acid.